Recognition-mediated activation of therapeutic gold nanoparticles inside living cells

Abstract

Supramolecular chemistry provides a versatile tool for the organization of molecular systems into functional structures and the actuation of these assemblies for applications through the reversible association between complementary components. Use of this methodology in living systems, however, represents a significant challenge owing to the chemical complexity of cellular environments and lack of selectivity of conventional supramolecular interactions. Herein, we present a host–guest system featuring diaminohexane-terminated gold nanoparticles (AuNP–NH2) and complementary cucurbit[7]uril (CB[7]). In this system, threading of CB[7] on the particle surface reduces the cytotoxicity of AuNP–NH2 through sequestration of the particle in endosomes. Intracellular triggering of the therapeutic effect of AuNP–NH2 was then achieved through the administration of 1-adamantylamine (ADA), removing CB[7] from the nanoparticle surface, causing the endosomal release and concomitant in situ cytotoxicity of AuNP–NH2. This supramolecular strategy for intracellular activation provides a new tool for potential therapeutic applications. Application of supramolecular chemistry in living systems is challenging because of the inherent chemical complexity of cellular environments. Now, the use of a carefully designed host–guest system featuring diaminohexane-terminated gold nanoparticles and complementary cucurbit[7]uril macrocycles has been shown to provide triggered activation of a therapeutic system in living cells.

Cite this article

Kim, C., Agasti, S., Zhu, Z. et al. Recognition-mediated activation of therapeutic gold nanoparticles inside living cells. Nature Chem 2, 962–966 (2010). https://doi.org/10.1038/nchem.858

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